GOVERNMENT & POLICY

PAVING THE WAY FOR NANOTECH Institute of Medicine roundtable hosts forum to assess field, find ways to avoid misconceptions SUSAN R. MORRISSEY, C&EN WASHINGTON

NANOTECHNOLOGY HAS BEEN

billed as the next great tech­nological revolution—some­times referred to as the "sec­ond Industrial Revolution." It

holds great promise in a number of areas, including medicine, energy, and materials science. But as the science advances and applications begin to emerge, researchers and policymakers fear that unintended health and environmental implications and a backlash of negative public opinion will stop the field in its tracks.

l b guard against such a backlash, a push is under way to make sure that, as the sci­ence moves forward, issues related to the environmental and safety implications and the ethical concerns of nanotechnology al­so are studied. This latter group of studies was the topic of discussion at an Institute of Medicine workshop held in Washing­ton, D.C., on May 27. Sponsored by IOM's Roundtable on Environmental Health Sci­ences, Research & Medicine, the meeting assessed the current state of research on nanotech implications.

"There are a number of uncertainties related to nanotechnology, but we've faced uncertainties before with emerging tech­nologies," roundtable Chairman Paul G.

Rogers, partner at Hogan & Hartson LLP, said at the opening of the workshop. He noted that the science community needs to make the science understandable so that informed policy decisions can be reached. To do this, communication will be key

"It's important to get the public involved up front," said Kenneth Olden, director of the National Institute of Environmental Health Sciences at the National Institutes of Health. "We should anticipate that not every nanomaterial that is made will be be­nign" and be on guard to prevent harmful materials from being released into the pub­lic, he noted.

The public must have access to the facts so that they can educate themselves, Old­en said. Otherwise, he added, they will not accept the resulting technological advances and will miss out on their benefits.

With the federal investment in nano­technology at nearly $ 1 billion per year, the nascent field is maturing and moving from the laboratory to the marketplace, where it is predicted to have a revolutionary im­pact. Nanotechnology is already being used to make products that include sunscreens, tennis balls, stain-resistant fabrics, and electroconductive coatings.

Currently the estimated total amount of

TO MARKET Zyvex is using its Kentera technology to bridge functional groups onto nanotubes, which can then be dispersed onto a host. This field-emission surface scanning electron microscope image shows a polyurethane thin-film composite loaded at 2.5 weight % with Kentera. The carbon nanotubes appear as white fibers retained in the matrix.

nanoparticles in commerce is a few thou­sand tons, reported Vicki L. Colvin, asso­ciate chemistry professor and executive director of the Center for Biological & En­vironmental Nanotechnology at Rice Uni­versity This is not a significant amount of material, but as future concepts such as high-tech battle suits (C&EN, Aug. 11, 2003, page 28) become realities, the quan­tity will grow, she explained.

ieWe are at an optimal time to study these problems," Colvin pointed out. iCWe are at the birth of a new market. We can shape this area with knowledge as it develops."

PERHAPS THE BIGGEST challenge in try­ing to shape the emerging market and in­form the public is the limited data on the toxicity and bioavailability of engineered nanoparticles, Olden said. For the avail­able environmental and health data to in­crease, a better toxicity screening process needs to be in place. "Toxicology assess­ments will be expensive and daunting un­less we can develop new strategies to iden­tify toxicity on a large scale, not on a single material as is now done," he said.

The small number of publications eval­uating the toxicity of engineered nanopar­ticles is evidence of the difficulty in screen­ing these materials. According to Colvin, only 50 peer-reviewed research papers on environmental and health effects of engi­neered nanoparticles have been published. The situation is better for naturally occur­ring nanoparticles, where Colvin noted that there are about 500 publications. By far, the most work in this area has been on in­cidental nanoparticles such as ultrafine soot and carbon black—forwhich there are more than 10,000 peer-reviewed publications.

The large number of papers on inci­dental nanoparticles came from industry studies looking at manufacturing by-prod­ucts, Colvin explained. These nanoparti­cles have a high concentration in the en­vironment and typically have a complex

We should anticipate that not every nanomaterial that is made will be benign." 2 6 C & E N / J U N E 14 , 2 0 0 4 H T T P : / / W W W . C E N - O N L I N E . O R G

composition, an ill-defined surface chem­istry and a diameter less than 100 nm.

In contrast, engineered nanoparticles are relatively new and are not yet present in the environment in high quantities. These particles also differ from incidental nanoparticles in that they are typically

Colvin Maynard

very pure in composition, have a controlled surface chemistry and are much smaller in diameter.

The novel properties of nanoparticles give rise to an important deviation from the

traditional paradigm of evaluating particles' health risks. "The current paradigm says that health effects associated with inhala­tion exposure to particles are related to the mass of the material depositing in the lung," said Andrew D. Maynard, senior service fel­low at the National Institute for Occupa­

tional Safety & Health. When it comes to nano­

particles, however, the fac­tors that contribute to the health risks include surface area, surface chemistry and size-deposition probability and translocation, Maynard said. "But these factors do not include particle mass," he pointed out. This obser­vation illustrates the need for a change in philosophy when dealing with nanopar­ticles, he said.

Another unique aspect of nanoparticles is their behavior, Colvin not­ed. Studies have shown that nanoparticles cannot be assumed to behave like a bulk material or a single molecule of the same composition, she explained. She also dis­

cussed three important lessons of nanopar­ticles' behavior that she has learned from the emerging data on fullerenes.

First, the physical size of nanoparticles is not constant, as they tend to form col­loidal aggregates. Another point is that the surface of the nanoparticle influences its properties, and derivatizing the sur­face can significantly alter the toxicity Fi­nally, the properties of the nanoparticle will change as its surface interacts with the environment.

THESE OBSERVATIONS illustrate how hard it can be to determine the toxicity of nanoparticles. Based on the limited pub­lished data, the relative toxicity of engi­neered nanoparticles is worrisome, said John M. Balbus, director of the Environ­mental Health Program at Environmental Defense—a nonprofit, environmental ac­tivist organization.

For example, Balbus noted that the da­ta available on fullerenes show that the par­ticles are translocated to the brain, cause membrane lipid peroxidation, and prevent bacterial growth in an aqueous aquarium environment (C&EN, April 5, page 14). In

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GOVERNMENT & POLICY

T A R G E T I N G T U M O R S

Nanomedicine Moves Beyond The Bench

A lthough most of the scientific talks at a recent Institute of Medicine fo­rum on implications of nanotech-

nology were devoted to precautionary tales of nanotech's negative impact on human health, University of Michigan en­vironmental health professor Martin A. Philbert gave attendees a glimpse of how nanomedicine could transform cancer di­agnosis and treatment.

Philbert has been developing a range of biological nanosensors called PEBBLEs (probes encapsulated by biologically local­ized embedding) in collaboration with Uni­versity of Michigan chemistry professor Raoul Kopelman (C&EN, Jan. 29, 2001, page 31). PEBBLEs are nanoprobes made

addition, he added, carbon nanotubes that have been placed directly into the tracheas of rats have been found to cause the ani­mals to suffocate (C&EN, April 28,2003, page 30). Thus far, scientific studies do not

of sensing molecules trapped in a chemi­cally inert matrix. They can be used to monitor various chemicals inside living cells without doing any damage

The researchers are cur­rently trying to make more so­phisticated PEBBLEs that go beyond sensing applications. The idea, Philbert says, is to make one PEBBLE that can

CHANGING COLORS PEBBLEs made with a ruthenium-based chelate kill rat glioma cells by generating singlet oxygen upon excitation with light. Dead cells appear red; living cells appear green.

paint a reassuring picture of the environ­mental and health safety of these engi­neered nanoparticles, he said.

Many more questions must be answered before the toxicity can be confidently de-

image a tumor and then, in a slightly dif­ferent mode, kill that tumor as noninva­sive^ as possible.

"The concept is simple, but the imple­mentation is very difficult," Philbert tells C&EN. Creating PEBBLEs that can safely perform such varied tasks, he says, is like

a battle between physics, chemistry, materials science, and biology: "In order to get a very good medical therapy, you have to conquer each of those domains and have them work together."

Despite the technical chal­lenge, the researchers have

already seen some promising in vivo re­sults using PEBBLEs to treat certain types of brain tumors in rats. They hope to publish the work within the next few months.-BETHANY HALF0RD

termined, Balbus noted. "What we don't know far exceeds what we do know," he said. In light of this, he questioned whether current Environmental Protection Agency regulations under the Toxic Substances

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Control Act (TSCA) are sufficient to han­dle the developing use of engineered nanoparticles.

Under TSCA, engineered nanoparticles are not viewed as new compounds unless they have a unique composition. For ex­ample, Ti02 nanoparticles are handled the same way with respect to regulation as bulk Ti02, even though the two forms have dif­ferent properties. This situation shows that new regulations need to be developed, Bal-bus said.

A model that could be used to regulate these novel materials is the one used by the European Commission, Balbus point­ed out. The commission uses an algorithm that gives nonsoluble particles a higher risk assessment priority because these parti­cles have the potential to bioaccumulate. Although the success of this proactive stance has yet to be demonstrated because it is still being implemented, it is an option worth considering, he explained.

Another model is to work within the existing regulatory framework until a new framework can be developed. This is what is happening in Canada, said Paul Glover, director general of the Safe Environments

Program at Health Canada. He noted that Canada is using horizontal management to address this problem, an approach where all the players—government, industry and researchers—work together not as indi­vidual departments and agencies but as a multidis-ciplinary team.

The U.S. is also taking steps to develop an effective framework for dealing with nanotechnology, noted E. ClaytonTeague, director of the National Nanotechnol­ogy Coordination Office at the National Nanotechnol­ogy Initiative. NNI —which provides a long-term R&D focus for nanotechnology and coordinates the relevant Balbus federal agencies in this area (C&EN, April 19, page 30)-is fundingre-search into the environmental and health implications of nanotechnology. About 11% of NNFs funding is beingused to study applications and implications in this area, he said.

Teague also said the federal agencies are

working together as part of the National Environmental & Health Implications working group to develop standards such as best practices and a common nomen­clature for the emerging field.

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"The train has yet to leave the station," Maynard told the audience. "We have the opportunity to work hand-in-hand with people in industry" to ensure that regula­tions and policies are developed that allow the public to get the maximum benefits of nanotechnology •

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